Method of using spinal cord stimulation to treat gastrointestinal and/or eating disorders or conditions

ABSTRACT

The present invention involves a method and a system for using electrical stimulation to treat gastrointestinal and/or eating disorders. More particularly, the method comprises surgically implanting an electrical stimulation lead that is in communication with predetermined thoracic vertebral segments to cause spinal nervous tissue stimulation, thus treating a wide variety of gastrointestinal disorders.

CROSS-REFERENCE TO RELATED APPLICATIONS

This Application is a continuation of U.S. application Ser. No.11/234,960, filed Sep. 26, 2005, pending, which claimed the benefit ofU.S. Provisional Application Nos. 60/613,495 filed Sep. 27, 2004 and60/614,312 filed Sep. 29, 2004, the disclosures of which are fullyincorporated herein by reference.

TECHNICAL FIELD

This invention relates to spinal cord stimulation for treatinggastrointestinal, disorders, eating disorders, and related conditions,including abdominal pain, gastroparesis, obesity, and pancreatitis.

BACKGROUND OF THE INVENTION

The gastrointestinal (“GI”) function is to process and consume food, toextract nutrients and to dispose of waste products of digestion. Thedigestive system is a twisted shaped tube that starts with the mouth,throat, gullet (esophagus), stomach, ileum (small intestine), colon(large intestine), rectum and anus. This muscular tube is some 25 feetlong with most of it coiled within the abdomen. The stomach is a complexorgan of the digestive tract (alimentary canal) with the primaryfunctions of dissolution, reduction, and motility of ingested food.Normal contractions of the stomach are the result of three controlcomponents: neural activity, chemical activity, and myogenic activity.The neural control component refers to the intrinsic and extrinsicnerves innervating the stomach.

Direct electrical stimulation of the stomach and other portions of thegastric intestinal tract has been experimented with for some time. Mostof the experimentation has been oriented toward improving the gastricemptying usually by attempting to speed up or strengthen/reinforce theperistaltic activity through directly placing stimulators on the musclesinvolved. For example, some of the work has centered on using directelectrical stimulation for the treatment of gastroparesis, or delayedstomach emptying, a condition that is most often a complication ofdiabetes. Seven million people in the United States may be affected bydiabetes, and up to 75% of diabetic patients may experiencegastrointestinal dysfunction, including diabetic gastroparesis, asyndrome of delayed gastric emptying, leading to nausea, vomiting,abdominal pain and early satiety.

U.S. Pat. No. 5,423,872 to Cigaina for “Process and Device for TreatingObesity and Syndromes Related to Motor Disorders of the Stomach of aPatient” issued Jun. 3, 1995, describes an implantable gastricelectrical stimulator at the antrum area of the stomach which generatessequential electrical pulses to stimulate the entire stomach, therebyartificially altering the natural gastric motility to prevent emptyingor slows down food transit through the stomach. U.S. Pat. No. 5,690,691to Chen et al. for “Gastro-intestinal Pacemaker Having PhasedMulti-Point Stimulation” issued Nov. 25, 1997, describes a portable orimplantable gastric pacemaker employing a number of electrodes along thegreater curvature of the stomach for delivering phased electricalstimulation at different locations to accelerate or attenuateperistaltic movement in the GI tract. U.S. Pat. No. 5,836,994 toBourgeois for “Method and Apparatus for Electrical Stimulation of theGastrointestinal Tract” issued Nov. 17, 1998, describes an implantablegastric stimulator which incorporates direct sensing of the intrinsicgastric electrical activity by one or more sensors of predeterminedfrequency bandwidth for application or cessation of stimulation based onthe amount of sensed activity. U.S. Pat. No. 6,091,992 to Bourgeois for“Method and Apparatus for Electrical Stimulation of the GastrointestinalTract” issued Jul. 18, 2000 relates to provision of separate electricalpulse trains of differing parameters wherein the pulse trains arecomposed of a series of at least two pulses. The therapy is applied topromote gastric peristalsis.

U.S. Pat. No. 6,104,955 to Bourgeois for “Method and Apparatus forElectrical Stimulation of the Gastrointestinal Tract” issued Aug. 15,2000, relates to a gastric stimulator with reversion to a sensing modeto determine the intrinsic slow wave interval to prevent stimulationwhen the gastric tract is in inter-digestive phases. U.S. Pat. No.5,861,014 to Familoni for “Method and Apparatus for Sensing aStimulating Gastrointestinal Tract On-Demand” issued Jan. 19, 1999,relates to an implantable gastric stimulator for sensing abnormalelectrical activity of the gastrointestinal tract so as to provideelectrical stimulation for a preset time period or for the duration ofthe abnormal electrical activity to treat gastric rhythm abnormalities.

Despite the attempts to modulate the gastrointestinal system via directelectrical stimulation, there are still several patients in which thistype of stimulation system does not provide relief from theirgastrointestinal and/or eating disorder. Thus, the present inventionprovides a novel method of using spinal cord stimulation to treatgastrointestinal and/or eating disorders or conditions.

BRIEF SUMMARY OF THE INVENTION

The present invention relates to stimulation techniques applied to areasof the spinal cord hot considered in the prior art to play a role ingastrointestinal and/or eating disorders. In certain embodiments, theinvention uses electrical stimulation to treat gastrointestinal and/oreating disorders.

In one embodiment, the invention provides a method of treating agastrointestinal and/or eating disorder or condition by stimulatingspinal nervous tissue at one or more areas associated with a thoracicvertebral segment. In certain embodiments of the invention, it iscontemplated that the stimulation is electrical, chemical, or acombination of both.

The gastrointestinal and/or eating disorder or condition may be furtherdefined as obesity, abdominal pain, pelvic pain, anorexia nervosa orbulimia nervosa, pancreatitis, Crohn's disease, or gastroparesis. In aspecific embodiment, the gastroparesis is associated with diabetes.

In another embodiment, the invention provides a method of treating apatient with a gastrointestinal and/or eating disorder or conditioncomprising the steps of: surgically implanting in the patient a systemin communication with spinal nervous tissue at one or more areasassociated with a thoracic vertebral segment of the spinal cord; andoperating the system to stimulate the spinal nervous, thereby treatingthe gastrointestinal disorder or condition.

In certain embodiments of the invention, it is contemplated thatstimulating spinal nervous tissue comprises stimulating spinal nervoustissue associated with at least one of 4^(th) thoracic vertebralsegment, the 5^(th) thoracic vertebral segment, the 6^(th) thoracicvertebral segment, the 7^(th) thoracic vertebral segment, the 8^(th)thoracic vertebral segment, or the 9^(th) thoracic vertebral segment.

In certain embodiments of the invention, the system comprises anelectrode. In specific embodiments of the invention, the stimulation iselectrical. It is envisioned that in one procedure for placing theelectrode portion of the stimulator lead, the stimulation lead isinserted or implanted in the epidural space at a thoracic level of thespinal cord.

In certain embodiments of the invention, the system comprises aninfusion pump in communication with spinal nervous tissue. In a specificembodiment, the methods of the present invention comprise surgicallyimplanting a catheter having a proximal end coupled to a pump and adischarge portion for infusing a dosage of a pharmaceutical, whereinafter implantation the discharge portion of the catheter is incommunication with spinal nervous tissue associated with a thoracicvertebral segment.

It is contemplated that, in certain embodiments of the invention, thesystem allows the patient to control the frequency of stimulation. Forexample, it is envisioned that the stimulating is prior to, during, orafter the patient consumes food. Thus, in certain embodiments, theelectrical spinal cord stimulation delivers electrical pulses on asubstantially continuous basis. Still further, the invention maycomprise an external handheld device (a “patient programmer”) can beused by the patient to wirelessly communicate with the implantedstimulator system to initiate the electrical stimulation at anappropriate time.

One embodiment of the present invention is a method of increasinggastric motility comprising the steps of: surgically implanting a systemin communication with spinal nervous tissue associated with one or morethoracic vertebral segments; and operating the system to stimulate thespinal nervous tissue, thereby affecting (i.e., increasing) gastricmotility.

Another embodiment of the present invention is a method of increasingglucagon-like peptide 1 activity in a patient comprising the steps of:surgically implanting in the patient a system in communication withspinal nervous tissue associated with one or more thoracic vertebralsegments; and operating the system to stimulate the spinal nervoustissue, thereby increasing glucagon-like peptide 1 activity.

It is also contemplated that the present invention provides a method oftreating a gastrointestinal disorder and/or condition comprising thesteps of: surgically implanting an electrical stimulation lead having aproximal end and a stimulation portion, wherein after implantation thestimulation portion is in communication with spinal nervous tissueassociated with one or more thoracic vertebral segments; coupling theproximal end of the lead to a signal generator; and generating anelectrical signal with the signal generator wherein said signalelectrically stimulates the spinal nervous, thereby treating thegastrointestinal disorder and/or condition.

In certain embodiments of the invention, the stimulating results inmodulation of gastric and/or gastrointestinal activity.

It is contemplated that the present invention provides a method andsystem of treating a wide variety of eating and/or gastrointestinaldisorders and/or conditions such as heartburn, bloating, postoperativeileus, abdominal pain and discomfort, early satiety, abdominal pain,epigastric pain, nausea, vomiting, burbulence, regurgitation, intestinalpseudoobstruction, anal incontinence, gastroesophageal reflux disease,irritable bowel syndrome, dyspepsia, chronic constipation,gastroparesis, ulcerative colitis, pancreatitis, Crohn's disease,menstrual cramps, spastic and interstitial cystitis and ulcers, obesity,anorexia nervosa, and bulimia nervosa.

In one embodiment, it is envisioned that the method of the presentinvention is useful for a patient has previously failed pharmaceuticaltherapy or direct gastric stimulation therapy for gastroparesis.

The present invention also provides a system for treating agastrointestinal disorder and/or condition comprising: a probe having astimulation portion in communication with spinal nervous tissueassociated with one or more thoracic vertebral; and a device tostimulate the probe thereby stimulating the spinal nervous, and treatingthe gastrointestinal disorder and/or condition.

Another embodiment of the invention is a system for treating subjectswith gastrointestinal disorders and/or conditions comprising: anelectrical stimulation lead that is implanted into the subject's spinal,the lead comprises at least one electrode that is in communication withspinal nervous tissue associated with one or more thoracic vertebralsegments; and a signal generator that generates signals for transmissionto the electrode of the lead resulting in delivery of electrical signalsto the spinal nervous tissue, thereby treating the gastrointestinaldisorder and/or conditions.

Yet further, another embodiment of the present invention comprises amethod of treating gastoparesis, comprising: implanting at least anelectrical lead within a patient such that at least one electrode of theelectrical lead is disposed adjacent to nerve tissue associated with athoracic vertebral segment; selecting a plurality of operatingparameters for an electrical spinal cord stimulation system that areeffective for treating gastoparesis; programming the electrical spinalcord stimulation system according to the plurality of operatingparameters; and activating the electrical spinal cord stimulation systemto deliver electrical pulses to the electrode adjacent to nerve tissueassociated with the thoracic vertebral segment thereby treating thepatient's gastoparesis. More specifically, the at least one electrode isdisposed within the T5/T6 epidural space of the patient.

The selecting step may comprise the steps of: temporarily deliveringelectrical pulses according to the plurality of operating parameters tothe electrode adjacent to nerve tissue associated with the thoracicvertebral segment; and monitoring gastric activity that occurs while thetemporarily delivering is performed, for example, determining gastricmotility by measuring pressure generated by contraction of muscles ofthe stomach and/or small intestine.

In further embodiments, the lead comprises a plurality of electrodes andthe plurality of operating parameters include an electrodeconfiguration. A plurality of operating parameters include a pulseamplitude parameter, a pulse width parameter, and a pulse frequencyparameter, for example, the pulse frequency parameter is within therange of 10-350 Hz.

Another embodiment comprises a method of treating an eating disorder,comprising: implanting at least an electrical lead within a patient suchthat at least one electrode of the electrical lead is disposed adjacentto nerve tissue associated with a thoracic vertebral segment; selectinga plurality of operating parameters for an electrical spinal cordstimulation system that are effective for treating the eating disorder;programming the electrical spinal cord stimulation system according tothe plurality of operating parameters; and activating the electricalspinal cord stimulation system to deliver electrical pulses to theelectrode adjacent to nerve tissue associated with the thoracicvertebral segment thereby treating the patient's eating disorder, forexample, obesity, anorexia nervosa, and bulimia nervosa.

In certain embodiments, the electrical spinal cord stimulation deliverselectrical pulses on a temporary basis in response to receiving aninitiation signal from an external control device operated by thepatient. The patient uses the external control device to deliverelectrical pulses beginning immediately before the patient beginseating, and stimulation of nerve tissue associated with the thoracicvertebral segment causes an increase in gastric motility.

The foregoing has outlined rather broadly the features and technicaladvantages of the present invention in order that the detaileddescription of the invention that follows may be better understood.Additional features and advantages of the invention will be describedhereinafter which form the subject of the claims of the invention. Itshould be appreciated that the conception and specific embodimentdisclosed may be readily utilized as a basis for modifying or designingother structures for carrying out the same purposes of the presentinvention. It should also be realized that such equivalent constructionsdo not depart from the invention as set forth in the appended claims.The novel features which are believed to be characteristic of theinvention, both as to its organization and method of operation, togetherwith further objects and advantages will be better understood from thefollowing description when considered in connection with theaccompanying figures. It is to be expressly understood, however, thateach of the figures is provided for the purpose of illustration anddescription only and is not intended as a definition of the limits ofthe present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of the present invention, reference isnow made to the following descriptions taken in conjunction with theaccompanying drawings.

FIGS. 1A and 1B illustrate example electrical stimulation systems.

FIGS. 2A-2I illustrate example electrical stimulation leads that may beused in the present invention.

FIGS. 3A and 3B illustrate a spinal cord diagram.

DETAILED DESCRIPTION OF THE INVENTION

It is readily apparent to one skilled in the art that variousembodiments and modifications can be made to the invention disclosed inthis Application without departing from the scope and spirit of theinvention.

I. Definitions

As used herein, the use of the word “a” or “an” when used in conjunctionwith the term “comprising” in the claims and/or the specification maymean “one,” but it is also consistent with the meaning of “one or more,”“at least one,” and “one or more than one.” Still further, the terms“having”, “including”, “containing” and “comprising” are interchangeableand one of skill in the art is cognizant that these terms are open endedterms.

The term “abdominal viscera disorder(s)” as used herein includes thosecondition which affect the smooth muscles of the lower abdomen outsideof the GI tract and include but are not limited to those conditionstreated by regulation, stabilization and normalization ofenterochromaffin cell secretory, pain and motility mechanisms, afferentfiber activity and GI and lower abdominal smooth muscle cells.

The term “constipation” as used herein means a condition characterizedby infrequent or difficult evacuation of feces resulting from conditionssuch as altered GI motility, altered sensation or evacuation functionsand altered reabsorption of water.

The term “dyspepsia” as used herein means a condition characterized bysymptoms of abdominal pain, epigastric pain, bloating, early satiety,nausea, heartburn and vomiting as a primary gastrointestinal dysfunctionor as a complication, and not exclusive to other disorders such asappendicitis, gallbladder disturbances, or malnutrition.

As used herein, the use of the words “epidural space” or “spinalepidural space” is known to one with skill in the art, and refers to anarea in the interval between the dural sheath and the wall of the spinalcanal. It is contemplated that stimulation leads may be implanted in theepidural space. As used herein, the term “subdural” refers to the spacebetween the dura matter and arachnoid membrane. In certain embodimentsof the invention, a stimulation lead may be implanted in the subduralspace.

As used in this disclosure, the term “gastrointestinal” and variationsof the term, refer to either the whole alimentary tract, including, forexample, the esophagus, stomach, duodenum, small intestine, largeintestine and rectum, or to any portion or portions of the alimentarytract, as will be understood by those with skill in the art withreference to this disclosure. The gastrointestinal altered motility,sensitivity and secretion and abdominal viscera disorders which may betreated with the above-identified methods and systems include heartburn,bloating, postoperative ileus, abdominal pain and discomfort, earlysatiety, epigastric pain, nausea, vomiting, burbulence, regurgitation,intestinal pseudoobstruction, anal incontinence, chronic constipation,diabetic gastroparesis, dyspepsia, gastroesophageal reflux disease,irritable bowel syndrome, ulcerative colitis, Crohn's disease, menstrualcramps, pancreatitis, spastic and interstitial cystitis and ulcers andthe visceral pain associated therewith.

The term “gastrointestinal disorder or conditions” as used hereinincludes gastrointestinal altered motility, sensitivity and secretiondisorders in which one or more of the symptoms and conditions affect thegastrointestinal tract from the mouth to the anus. Gastrointestinaldisorders include, but are not limited to, heartburn, bloating,postoperative ileus, abdominal pain and discomfort, early satiety,epigastric pain, nausea, vomiting, burbulence, regurgitation, intestinalpseudoobstruction, anal incontinence, gastroesophageal reflux disease,irritable bowel syndrome, ulcerative colitis, Crohn's disease, renaldisorders, menstrual cramps, pancreatitis, spastic and interstitialcystitis and ulcers and the visceral pain associated therewith. One withskill in the art is aware that any functional gastrointestinal disorder,including but not limited to those associated with gastric motility, isappropriate for treatment with the method and systems of the presentinvention.

The term “gastroesophageal reflux disease” and “GERD” as used hereinmeans the incidence of, and the symptoms of, those conditions caused bythe reflux of the stomach contents into the esophagus. This includes allforms/manifestations of GERD including, but not limited to, erosive andnon-erosive GERD, heartburn and other symptoms associated with GERD.

The term “gastroparesis” as used herein means a paralysis of the stomachbrought about by a motor abnormality in the stomach which is oftenmanifested as delayed gastric emptying. This can also be a complicationof diseases such as diabetes, progressive systemic sclerosis, anorexianervosa, or myotonic dystrophy. Although diabetes is the most commonknown cause, gastroparesis can be the result of physical problems,medications, as well as metabolic, smooth muscle and nervous systemdisorders. For example, physical problems leading to gastroparesis caninclude scarring from tumors and ulcers, as well as surgery on the vagusnerve or stomach. Certain medications, including Cardizem and othercalcium blockers, which slow contractions in the intestine or weaken thestomach, can contribute to gastroparesis. Hypothyroidism is an exampleof a metabolic disorder associated with gastroparesis. Smooth muscledisorders such as amyloidosis and scleroderma can cause gastroparesis,as can disorders of the nervous system, such as Parkinson's disease andabdominal migraine.

As used herein, the term “in communication” refers to the stimulationlead being adjacent, in the general vicinity, in close proximity, ordirectly next to or directly on the predetermined stimulation site, suchas a level or area of the spinal cord associated with thoracic vertebralsegments. Thus, one of skill in the art understands that the lead is “incommunication” with the nervous tissue or spinal cord associated with athoracic vertebral segment if the stimulation results in a modulation ofneuronal activity resulting in the desired response, such as modulationof the gastrointestinal and/or eating disorder.

The term “irritable bowel syndrome” and “IBS” as used herein means adisorder of function involving altered motility, sensitivity andsecretion involving the small intestine and large bowel associated withvariable degrees of abdominal pain, constipation, bloating or diarrheawithout bowel inflammation.

The term “ischemic colitis” refers to inflammation of the largeintestine (colon) caused by decreased blood flow to the colon.

The terms “mammal,” “mammalian organism,” “subject,” or “patient” areused interchangeably herein and include, but are not limited to, humans,dogs, cats, horses and cows. The preferred patients are humans.

As used herein the term “modulate” refers to the ability to regulatepositively or negatively neuronal activity, including but not limitedto, neuronal activity via stimulation of the spinal cord or spinalnervous tissue associated with the thoracic vertebral segments whichinnervates the organs of the abdominal cavity (e.g., stomach, pancreas,spleen, gall bladder, liver, small intestine, large intestine, kidney,or any other tissue associated with the abdominal cavity), as well asthe esophagus. Further, the term modulate can be used to refer to anincrease, decrease, masking, altering, overriding or restoring neuronalactivity, including but not limited to, neuronal activity associatedwith the thoracic nerve roots. Modulation of neuronal activity, such asthat associated with the thoracic nerve roots, can affect pain and/orgastric activity or gastric motility of a subject, abdominal pain,intestinal motility, esophageal motility, among other effects.

As used herein, the term “neuronal” refers to a neuron which is amorphologic and functional unit of the brain, spinal column, andperipheral nerves.

As used herein, the term “pharmaceutical” refers to a chemical or agentthat is used as a drug. Thus, the term pharmaceutical and drug areinterchangeable.

As used herein, the term “stimulate” or “stimulation” refers toelectrical and/or chemical modulation of selected thoracic nervoustissue, thoracic nerve roots, thoracic segments, thoracic levels, orareas of the spinal cord associated with a thoracic vertebral segment.

The phrase “spinal cord stimulation” as used herein includes stimulationof any spinal nervous tissue, including spinal neurons, accessoryneuronal cells, nerves, nerve roots, nerve fibers, or tissues, that areassociated with the spinal cord. It is contemplated that spinal cordstimulation may comprise stimulation of one or more areas associatedwith a thoracic vertebral segment.

As used herein, “spinal nervous tissue” refers to nerves, neurons,neuroglial cells, glial cells, neuronal accessory cells, nerve roots,nerve fibers, nerve rootlets, parts of nerves, nerve bundles, mixednerves, sensory fibers, motor fibers, dorsal root, ventral root, dorsalroot ganglion, spinal ganglion, ventral motor root, general somaticafferent fibers, general visceral afferent fibers, general somaticefferent fibers, general visceral efferent fibers, grey matter, whitematter, the dorsal column, the lateral column, and/or the ventral columnassociated with the spinal cord. Spinal nervous tissue includes “spinalnerve roots,” which comprise the 31 pairs of nerves that emerge from thespinal cord. Spinal nerve roots may be cervical nerve roots, thoracicnerve roots, and lumbar nerve roots.

As used herein, “spinal nervous tissue associated with a thoracicvertebral segment,” or “nervous tissue associated with a thoracicvertebral segment” or “spinal cord associated with a thoracic segment orlevel” includes any spinal nervous tissue associated a thoracicvertebral level or segment, which can include at least one thoracicnerve root and tissue associated therewith. Those of skill in the artare aware that the spinal cord and tissue associated therewith areassociated with cervical, thoracic and lumbar vertebrae. In the presentinvention, the spinal cord or spinal tissue that is stimulated isassociated with at least one or more of the 12 thoracic vertebra. Seealso FIGS. 3A and 3B. As used herein, T1 refers to thoracic vertebralsegment 1, T2 refers to thoracic vertebral segment 2, T3 refers tothoracic vertebral segment 3, T4 refers to thoracic vertebral segment 4,T5 refers to thoracic vertebral segment 5, T6 refers to thoracicvertebral segment 6, T7 refers to thoracic vertebral segment 7, T8refers to thoracic vertebral segment 8, T9 refers to thoracic vertebralsegment 9, T10 refers to thoracic vertebral segment 10, T11 refers tothoracic vertebral segment 11, and T12 refers to thoracic vertebralsegment 12, unless otherwise specifically noted.

As used herein, “thoracic nerve roots,” “nerves or nerve rootsassociated with a thoracic vertebral segment,” or “nerve rootsassociated with a thoracic vertebral level,” refer to nerves associatedwith levels, or segments of the thoracic vertebrae. Thoracic nerve rootsare numbered according to the vertebrae below which they emerge. Thus,one with skill in the art realizes that the T5 nerve root emergesbetween the T5 vertebra and T6 vertebra, and the T6 nerve root emergesbetween the T6 vertebra and T7 vertebra, and so on. One with skill inthe art realizes that due to aberrants (missing ribs) or geneticvariations, the exiting of the nerve may be altered in individualsubjects, and the above serves as a general guideline.

As used herein, the term “treating” and “treatment” refers tostimulating certain nervous tissue of the spinal cord so that thesubject has an improvement in the disease, for example, beneficial ordesired clinical results. For purposes of this invention, beneficial ordesired clinical results include, but are not limited to, alleviation ofsymptoms, alleviation of pain, diminishment of extent of disease,stabilized (i.e., not worsening) state of disease, delay or slowing ofdisease progression, amelioration or palliation of the disease state,and remission (whether partial or total), whether detectable orundetectable. One of skill in the art realizes that a treatment mayimprove the disease condition, but may not be a complete cure for thedisease.

II. Electrical Stimulation Systems

In general terms, stimulation system 10 includes an implantable pulsegenerator or stimulation source 12 and an implantable electrode, i.e.,an electrical stimulation lead, 14 for applying the stimulation signalto the target the spinal cord. In operation, both of these primarycomponents are implanted in the person's body. Stimulation source 12 iscoupled to a connecting portion 16 of electrical stimulation lead 14.Stimulation source 12 controls the electrical signals transmitted toelectrodes 18 located on a stimulating portion 20 of electricalstimulation lead 14, located adjacent the target thoracic segment,according to suitable signal parameters (e.g., duration, intensity,frequency, etc.). A doctor, the patient, or another user of stimulationsource 12 may directly or indirectly input signal parameters forcontrolling the nature of the electrical stimulation provided. Whetherstimulation source 12 is coupled directly to or embedded within thestimulation lead 14, stimulation source 12 controls the stimulationpulses transmitted to one or more stimulation electrodes 18 located on astimulating portion 20 of stimulation lead 14, positioned incommunication with a predetermined site to stimulatespinal nervoustissue, according to suitable stimulation parameters (e.g., duration,amplitude or intensity, frequency, pulse width, etc.).

In one embodiment, as shown in FIG. 1A, stimulation source 12 includesan implantable pulse generator (IPG). One of skill in the art is awarethat any commercially available implantable pulse generator can be usedin the present invention, as well as a modified version of anycommercially available pulse generator. Thus, one of skill in the artwould be able to modify an IPG to achieve the desired results. Anexemplary IPG is one that is manufactured by Advanced NeuromodulationSystems, Inc., such as the Genesis® System, part numbers 3604, 3608,3609, and 3644. Another example of an IPG is shown in FIG. 1B, whichshows stimulation source 12 including an implantable wireless receiver.An example of a wireless receiver may be one manufactured by AdvancedNeuromodulation Systems, Inc., such as the Renew® System, part numbers3408 and 3416. The wireless receiver is capable of receiving wirelesssignals from a wireless transmitter 22 located external to the person'sbody. The wireless signals are represented in FIG. 1B by wireless linksymbol 24. A doctor, the patient, or another user of stimulation source12 may use a controller 26 located external to the person's body toprovide control signals for operation of stimulation source 12.Controller 26 provides the control signals to wireless transmitter 22,wireless transmitter 22 transmits the control signals and power to thewireless receiver of stimulation source 12, and stimulation source 12uses the control signals to vary the signal parameters of electricalsignals transmitted through electrical stimulation lead 14 to thestimulation site. Thus, the external controller 26 can be for example, ahandheld programmer, to provide a means for programming the IPG. Anexample wireless transmitter 122 may be one manufactured by AdvancedNeuromodulation Systems, Inc., such as the Renew® System, part numbers3508 and 3516.

FIGS. 2A-2I illustrate example stimulation leads 14 that may be used forelectrically stimulating the spinal nervous tissue. As described above,each of the one or more stimulation leads 14 incorporated in stimulationsystem 10 includes one or more stimulation electrodes 18 adapted to bepositioned in communication with the predetermined site of the spinalcord and used to deliver to the stimulation pulses received fromstimulation source 12. A percutaneous stimulation lead 14, such asexample stimulation leads 14A-D, includes one or more circumferentialelectrodes 18 spaced apart from one another along the length ofstimulating portion 20 of stimulation lead 14. Circumferentialelectrodes 18 emit electrical stimulation energy generally radially(i.e., generally perpendicular to the axis of stimulation lead 14) inall directions. A laminotomy, paddle, or surgical stimulation lead 14,such as example stimulation leads 14E-I, includes one or moredirectional stimulation electrodes 18 spaced apart from one anotheralong one surface of stimulation lead 14. Directional stimulationelectrodes 18 emit electrical stimulation energy in a directiongenerally perpendicular to the surface of stimulation lead 14 on whichthey are located. Although various types of stimulation leads 14 areshown as examples, the present invention contemplates stimulation system10 including any suitable type of stimulation lead 14 in any suitablenumber. In addition, stimulation leads 14 may be used alone or incombination.

In one embodiment, the stimulation source is transcutaneously incommunication with the electrical stimulation lead. In “transcutaneous”,electrical nerve stimulation (TENS) the stimulation source is externalto the patient's body, and may be worn in an appropriate fanny pack orbelt, and the electrical stimulation lead is in communication with thestimulation source, either remotely or directly. In another embodiment,the stimulation is percutaneous. In “percutaneous” electrical nervestimulation (PENS), needles are inserted to an appropriate depth aroundor immediately adjacent to a predetermined stimulation site, and thenstimulated.

It is envisaged that the patient will require intermittent assessmentwith regard to patterns of stimulation. Different electrodes on the leadcan be selected by suitable computer programming, such as that describedin U.S. Pat. No. 5,938,690, which is incorporated by reference here infull. Utilizing such a program allows an optimal stimulation pattern tobe obtained at minimal voltages. This ensures a longer battery life forthe implanted systems.

Whether using percutaneous leads, laminotomy leads, or some combinationof both, the leads are coupled to one or more conventionalneurostimulation devices, or signal generators. The devices can betotally implanted systems and/or radio frequency (RF) systems. Anexample of an RF system is a Renew® system manufactured by AdvancedNeuromodulation Systems, Inc.

In one embodiment of the invention, stimulation systems that combine apulse generator and electrodes for tissue stimulation in a single systemmay be used. The Bion® stimulator is an example of one such systems thatare known in the art. A contemplated stimulation system may have noleads, with the electrodes directly connected to the pulse generator.Alternatively, in another embodiment, a stimulation system with flexibleleads is also contemplated. One with skill in the art realizes that themethods of the present invention are appropriate for use with anystimulation device capable of providing stimulation to spinal nervoustissue.

The preferred neurostimulation systems should allow each electrode ofeach lead to be defined as a positive, a negative, or a neutralpolarity. For each electrode combination (i.e., the defined polarity ofat least two electrodes having at least one cathode and at least oneanode), an electrical signal can have at least a definable amplitude(i.e., voltage), pulse width, and frequency, where these variables maybe independently adjusted to finely select the sensory transmittingnerve tissue required to inhibit transmission of neuronal signals.Generally, amplitudes, pulse widths, and frequencies are determinable bythe capabilities of the neurostimulation systems. Signal frequencies forthis application may be between 10-25,000 Hz, and in one embodimentapproximately 50 Hz-3,000 Hz, and in a preferred embodiment between10-350 Hz.

It is envisaged that the patient will require intermittent assessmentwith regard to patterns of stimulation. Different electrodes on the leadcan be selected by suitable computer programming, such as that describedin U.S. Pat. No. 5,938,690, which is incorporated by reference in itsentirety. Utilizing such a program allows an optimal stimulation patternto be obtained at minimal voltages. This ensures a longer battery lifefor the implanted systems.

III. Implantation of Electrical Stimulation Systems

Pain-managing or disease-managing electrical energy is commonlydelivered through electrodes positioned external to the dura layersurrounding the spinal cord. Stimulation on the surface of the cord(subdurally) is also contemplated, for example, stimulation may beapplied to the dorsal columns as well as to the dorsal root entry zone.The electrodes are carried by two primary vehicles: a percutaneous leadsand a laminotomy lead. Percutaneous leads commonly have two or more,equally-spaced electrodes, which are placed above the dura layer throughthe use of a Touhy-like needle. For insertion, the Touhy-like needle ispassed through the skin, between desired vertebrae, to open above thedura layer. For unilateral pain, percutaneous leads are positioned on aside of a dorsal column corresponding to the “afflicted” side of thebody, as discussed above, and for bilateral pain, a single percutaneouslead is positioned along the patient midline (or two or more leads arepositioned on each side of the midline). An example of aneight-electrode percutaneous lead is an OCTRODE® lead manufactured byAdvanced Neuromodulation Systems, Inc.

Laminotomy leads have a paddle configuration and typically possess aplurality of electrodes (for example, two, four, eight, or sixteen)arranged in one or more columns. An example of a sixteen-electrodelaminotomy lead is shown in FIG. 2.

Implanted laminotomy leads are commonly transversely centered over thephysiological midline of a patient. In such position, multiple columnsof electrodes are well suited to address both unilateral and bilateralpain, where electrical energy may be administered using either columnindependently (on either side of the midline) or administered using bothcolumns to create an electric field which traverses the midline. Amulti-column laminotomy lead enables reliable positioning of a pluralityof electrodes, and in particular, a plurality of electrode columns thatdo not readily deviate from an initial implantation position.

Laminotomy leads require a surgical procedure for implantation. Thesurgical procedure, or partial laminectomy, requires the resection andremoval of certain vertebral tissue to allow both access to the dura andproper positioning of a laminotomy lead. The laminotomy lead offers amore stable platform, which is further capable of being sutured inplace, that tends to migrate less in the operating environment of thehuman body. Unlike the needle-delivered percutaneous leads, laminotomyleads have a paddle configuration. The paddle typically possess aplurality of electrodes (for example, two, four, eight, or sixteen)arranged in some pattern, for example, columns. An example of aneight-electrode, two column laminotomy lead is a LAMITRODE® 44 leadmanufactured by Advanced Neuromodulation Systems, Inc. In the context ofconventional spinal cord stimulation, the surgical procedure, or partiallaminectomy, requires the resection and removal of certain vertebraltissue to allow both access to the dura and proper positioning of alaminotomy lead. Depending on the position of insertion, however, accessto the dura may only require a partial removal of the ligamentum flavumat the insertion site. In a preferred embodiment, two or more laminotomyleads are positioned within the epidural space of T5/T6 or T6/T7 orT7/T8 or T8/T9. The leads may assume any relative position to oneanother.

One technique that offers the ability to affect neuronal function is thedelivery of electrical stimulation for neuromodulation directly totarget tissues via an implanted system having a probe. Another techniquethat offers the ability to affect neuronal function is the delivery ofelectrical stimulation for neuromodulation directly to target tissuesvia an implanted system having a stimulation lead. The electrodeassembly of the stimulation system may be one electrode, multipleelectrodes, or an array of electrodes in or around the target area. Theproximal end of the probe or lead is coupled to the system to stimulatethe target site. Thus, the probe or lead is coupled to an electricalsignal source which, in turn, is operated to stimulate the predeterminedtreatment site.

IV. Infusion Pumps

In further embodiments, it may be desirable to use a drug deliverysystem independent of or in combination with the electrical stimulationsystems described herein. Drug delivery may be used independent of or incombination with a lead/electrode to provide electrical stimulation andchemical stimulation. When used, the drug delivery catheter is implantedsuch that the proximal end of the catheter is coupled to a pump and adischarge portion for infusing a dosage of a pharmaceutical or drug.Implantation of the catheter can be achieved by combining data from anumber of sources including CT, MRI or conventional and/or magneticresonance angiography into the stereotactic targeting model. Thus,without being bound to a specific procedure, implantation of thecatheter can be achieved using similar techniques as discussed above forimplantation of electrical leads, which is incorporated herein. Thedistal portion of the catheter can have multiple orifices to maximizedelivery of the pharmaceutical while minimizing mechanical occlusion.The proximal portion of the catheter can be connected directly to a pumpor via a metal, plastic, or other hollow connector, to an extendingcatheter.

Any type of infusion pump can be used in the present invention. Forexample, “active pumping” devices or so-called peristaltic pumps aredescribed in U.S. Pat. Nos. 4,692,147, 5,840,069, and 6,036,459, whichare incorporated herein by reference in their entirety. Peristalticpumps are used to provide a metered amount of a drug in response to anelectronic pulse generated by control circuitry associated within thedevice. An example of a commercially available peristaltic pump isSynchroMed® implantable pump from Medtronic, Inc., Minneapolis, Minn.

Other pumps that may be used in the present invention includeaccumulator-type pumps, for example certain external infusion pumps fromMinimed, Inc., Northridge, Calif. and Infusaid® implantable pump fromStrato/Infusaid, Inc., Norwood, Mass. Passive pumping mechanisms can beused to release an agent in a constant flow or intermittently or in abolus release. Passive type pumps include, for example, but are notlimited to gas-driven pumps described in U.S. Pat. Nos. 3,731,681 and3,951,147; and drive-spring diaphragm pumps described in U.S. Pat. Nos.4,772,263, 6,666,845, 6,620,151 which are incorporated by reference inits entirety. Pumps of this type are commercially available, forexample, Model 3000® from Arrow International, Reading, Pa. and IsoMed®from Medtronic, Inc., Minneapolis, Minn.; AccuRx® pump from AdvancedNeuromodulation Systems, Inc., Plano, Tex.

In certain embodiments, the catheter can be in the form of a leadcatheter combination, similar to the ones described in U.S. Pat. No.6,176,242 and U.S. Pat. No. 5,423,877, which are incorporated herein byreference in their entirety.

V. Combination Treatment

In order to increase the effectiveness of the electrical stimulationmethod of the present invention, it may be desirable to combineelectrical stimulation with chemical stimulation to treat thegastrointestinal and/or eating disorders.

In one preferred alternative, an implantable signal generator andelectrical stimulating lead and an implantable pump and catheter(s) areused to deliver electrical stimulation and/or one or more stimulatingdrugs to the above mentioned areas as a treatment for gastrointestinaland/or eating disorders.

Herein, stimulating drugs comprise medications, anesthetic agents,synthetic or natural peptides or hormones, neurotransmitters, cytokinesand other intracellular and intercellular chemical signals andmessengers, and the like. In addition, certain neurotransmitters,hormones, and other drugs are excitatory for some tissues, yet areinhibitory to other tissues. Therefore, where, herein, a drug isreferred to as an “excitatory” drug, this means that the drug is actingin an excitatory manner, although it may act in an inhibitory manner inother circumstances and/or locations. Similarly, where an “inhibitory”drug is mentioned, this drug is acting in an inhibitory manner, althoughin other circumstances and/or locations, it may be an “excitatory” drug.In addition, stimulation of an area herein includes stimulation of cellbodies and axons in the area.

Similarly, excitatory neurotransmitter agonists (e.g., norepinephrine,epinephrine, glutamate, acetylcholine, serotonin, dopamine), agoniststhereof, and agents that act to increase levels of an excitatoryneurotransmitter(s) (e.g., edrophonium; Mestinon; trazodone; SSRIs(e.g., flouxetine, paroxetine, sertraline, citalopram and fluvoxamine);tricyclic antidepressants (e.g., imipramine, amitriptyline, doxepin,desipramine, trimipramine and nortriptyline), monoamine oxidaseinhibitors (e.g., phenelzine, tranylcypromine, isocarboxasid)),generally have an excitatory effect on neural tissue, while inhibitoryneurotransmitters (e.g., dopamine, glycine, and gamma-aminobutyric acid(GABA)), agonists thereof, and agents that act to increase levels of aninhibitory neurotransmitter(s) generally have an inhibitory effect.(Dopamine acts as an excitatory neurotransmitter in some locations andcircumstances, and as an inhibitory neurotransmitter in other locationsand circumstances.) However, antagonists of inhibitory neurotransmitters(e.g., bicuculline) and agents that act to decrease levels of aninhibitory neurotransmitter(s) have been demonstrated to excite neuraltissue, leading to increased neural activity. Similarly, excitatoryneurotransmitter antagonists (e.g., prazosin, and metoprolol) and agentsthat decrease levels of excitatory neurotransmitters may inhibit neuralactivity. Yet further, lithium salts and anesthetics (e.g., lidocane)may also be used in combination with electrical stimulation.

VI. Gastrointestinal Motility

In certain embodiments of the invention, it is contemplated thatstimulation of spinal nervous tissue associated with one or morethoracic vertebral segments modulates gastric motility. In certainembodiments of the invention, esophageal, stomach, small intestinal,and/or large intestinal motility is altered.

Modulation of esophageal motility may involve the gastroesophagealjunction, and in particular the lower esophageal sphincter (LES), whichis an involuntary ring-like muscle separating the esophagus from thestomach. The LES rests in a closed position to shut off the end of theesophagus, and is relaxed when in the open state. However, the LES doesnot have the motility to open on its own, rather it opens briefly bynormal physiological function of the esophagus during excitation of theinhibitory nerves of the esophagus. This most commonly occurs duringperistalsis when the LES opens to allow food to pass from the esophagusto the stomach. Contracting nerves retum the LES to its normally closedposition.

Modulation of esophageal motility may be useful for the treatment ofdisorders such as gastroesophageal reflux disease, stricture, achalasia,diffuse esophageal spasm, esophageal cancer and dysphagia. Theseesophageal disorders affect the motility of the LES and thereby itsability to open and close normally.

Motility disorders of the esophagus, including those associated withsystemic disease such as that of the connective tissue, are normallydiagnosed using manometry, may be treated by modulation of the functionof the esophageal body, including modulation of peristaltic presence,propagation and vigor, or nonperistaltic contractions, as well as thatof the upper and lower esophageal

Normal contractions of the stomach are the result of three controlcomponents: neural activity, chemical activity, and myogenic activity.The neural control component refers to the intrinsic and extrinsicnerves innervating the stomach. The intrinsic nerves release variousneurotransmitters and peptides that control contractions and motility.In certain embodiments of the invention, extrinsic nerves may influencethe contractions by the release of modulative substances. The chemicalcontrol component refers to the various substances (neurotransmitters,neuromodulators and peptides) released from the nerve endings orendocrine-paracrine cells and glands of the stomach, gall-bladder, orpancreas. These biochemical substances may act directly on the smoothmuscle cell or on the nerves to modulate or control the occurrence ofcontractions and motility. The myogenic control component refers tosmall electrical oscillations of the smooth muscle cells related topolarization and depolarization of the smooth muscle cells. The myogenicactivity is referred to as electrical control activity or slow waves. Inthe present invention, it is contemplated that modulation of gastricmotility may be accomplished by modulating any of the above gastriccontrol components. In a preferred embodiment of the invention, one ormore of the above processes are modulated by the methods of the presentinvention.

Small intestinal motility during digestion comprises segmentationcontractions and peristalsis. The interdigestive state is seen betweenmeals, when the lumen is largely devoid of contents. During such times,so-called housekeeping contractions propagate from the stomach throughthe entire small intestine, sweeping it clear of debris. This complexpattern of motility is also known as the migrating motor complex.Motility in the small intestine, as in all parts of the digestive tube,is controlled predominantly by excitatory and inhibitory signals fromthe enteric nervous system. These local nervous signals are howevermodulated by inputs from the central nervous system, and a number ofgastrointestinal hormones appear to affect intestinal motility to somedegree

In the large intestine, the motility patterns comprise segmentationcontractions antiperistaltic contractions which propagate toward theileum, and peristaltic contractions, in addition to influx from thesmall intestine, facilitate movement of ingesta through the colon. Massmovements constitute a type of motility not seen elsewhere in thedigestive tube. Known also as giant migrating contractions, this patternof motility is like a very intense and prolonged peristaltic contractionwhich strips an area of large intestine clear of contents.

In periods between meals, the colon is generally quiescent. Following ameal, colonic motility increases significantly, due to signalspropagated through the enteric nervous system—the so called gastrocolicand duodenocolic reflexes, which are manifestation of enteric nervoussystem control. Additionally, distension of the colon is a primarystimulator of contractions. Several times each day, mass movements pushfeces into the rectum. This is largely a spinal reflex, and results inreflex relaxation of the internal anal sphincter followed by voluntaryrelaxation of the external anal sphincter and defecation.

For example, it is contemplated that spinal cord stimulation of one ormore areas associated with a thoracic segment is associated with anincrease in gastric motility or gastric activity. In another embodiment,it is contemplated that spinal cord stimulation of nervous tissueassociated with one or more areas associated with a thoracic segmentwill cause an increase in expression of neurotransmitters,neuromodulators and peptides or hormones associated with increasedgastric motility. In another embodiment, it is contemplated that spinalcord stimulation of nervous tissue associated with one or more areasassociated with a thoracic segment will cause an increase in expressionof neurotransmitters, neuromodulators or peptides associated with afeeling of fullness, for example glucagon-like peptide-1 (GLP-1). Inanother embodiment of the invention, it is contemplated that spinal cordstimulation of nervous tissue associated with one or more areasassociated with a thoracic segment is associated with modulatinggastric, activity by modulating gastric secretions, such as gastrichormones and enzymes. In one embodiment of the invention, modulation ofgastric motility comprises increasing the levels or activity of gastrin.

VII. Methods to Treat Gastrointestinal and/or Eating Disorders andConditions

Methods of spinal cord stimulation to alleviate pain are well known inthe art, particularly for use in treating back pain. However, methods ofstimulating spinal nervous tissue associated with one or more thoracicsegments in order to treat a gastrointestinal and/or eating disorder arenot known in the art, and are, in fact, contrary to conventional wisdomin the art. For example, Kemler et al. reported that spinal cordstimulation was associated with a relapse of ulcerative colitis in apatient in remission. Removal of the stimulator caused the patient to goback into remission. Additionally, other researchers have reported nogastric motility benefits to stimulating the areas of the spinal cordassociated with thoracic vertebral segments.

The present invention provides a novel method of treating agastrointestinal and/or eating disorders and conditions by stimulatingneuronal tissue associated with a thoracic vertebral segment. Forexample, a patient with gastroparesis was treated with spinal cordstimulation of spinal cord or neuronal tissue associated with a thoracicvertebral segment. This patient was recipient of a gastric pacemaker inan attempt to alleviate the patient's symptoms. The gastric pacemakerfailed to alleviate the patient's gastroparesis. After the gastricpacemaker was removed, a stimulation system as described was placed inaccording with the present invention and as is known to those skilled inthe art. The stimulation system was implanted and delivered electricalstimulation to spinal cord or neuronal tissue associated with a thoracicvertebral segment. The stimulation relieved the pain associated with thepatient's condition, which was unexpected because of the source of thepain, and it treated the patient's nausea and other gastroparesissymptoms, which may be surprising to those skilled in the art. Thestimulation also increased the patient's gastric motility, which hasallowed the patient to have a normal digestion and bowel movements.Based on the success of using such stimulation methods and systems, thevarious embodiments of the present invention discussed herein have beenconceived and reduced to practice.

In another embodiment, a patient with ulcerative colitis is implantedwith a stimulation system as described herein. The stimulation systemprovides stimulation on demand, as needed by the patient. The patientactivates the stimulation system when any pain or nausea is experienced.The patient has increased gastric motility and decreased pain or nauseasassociated with ulcerative colitis. The patient is able to normalizebowel function.

In another embodiment, a morbidly obese patent is implanted with astimulation system as described herein. The stimulation system isactivated just prior to, during or after the ingestion of food. Thepatient experiences increased gastric motility, which aids digestion. Inthis embodiment the patient may have increased levels of GLP-1, whichcontributes to a feeling of satiety.

In another embodiment, an underweight patient suffering from anorexianervosa is implanted with a stimulation system as described herein. Thestimulation system is activated as necessary in order to stimulategastric activity. The stimulation relieves constipation and normalizesgastric activity. Certain embodiments of the present invention involve amethod of treating a gastrointestinal disorder comprising the steps of:surgically implanting an electrical stimulation lead having a proximalend and a stimulation portion, wherein after implantation thestimulation portion is in communication with a predetermined site;coupling the proximal end of the lead to a signal generator; andgenerating an electrical signal with the signal generator to modulatethe predetermined site thereby treating the gastrointestinal disorder.

In certain embodiments, the predetermined site can include one or moreareas of the spinal cord or neuronal tissue associated with a thoracicvertebral segment, which innervates the organs of the abdominal cavity(e.g., stomach, pancreas, gall bladder, spleen, small intestine, largeintestine, liver, kidney), as well as the esophagus. Exemplary sitesincludes, the neuronal tissue associated with at least one or more ofthe thoracic vertebral segments 5-10 (T5, T6, T7, T8, T9, or T10) or anyvariation thereof such as between segments superior to T5, T5/T6, T6/T7,T7/T8, T8/T9, T9/T10, or inferior T10.

The gastrointestinal disorders or conditions contemplated by the presentinvention include gastrointestinal, altered motility, sensitivity andsecretion disorders in which one or more of the symptoms and conditionsaffect the gastrointestinal tract from the mouth to the anus.Gastrointestinal disorders include, but are not limited to, heartburn,bloating, postoperative ileus, abdominal pain and discomfort, earlysatiety, epigastric pain, nausea, vomiting, burbulence, regurgitation,intestinal pseudoobstruction, anal incontinence, gastroesophageal refluxdisease, irritable bowel syndrome, ulcerative colitis, Crohn's disease,menstrual cramps, pancreatitis, spastic and interstitial cystitis andulcers and the visceral pain associated therewith. One with skill in theart is aware that any functional gastrointestinal disorder, includingbut not limited to those associated with gastric motility, isappropriate for treatment with the method and systems of the presentinvention.

The present invention is also appropriate for treating a variety ofeating disorders and conditions, including obesity, anorexia nervosa,and bulimia nervosa. For example, it is contemplated that the method ofthe present invention may be used to treat patient for obesity, bingeeating, or compulsive overeating. A stimulator as described herein canbe implanted in the patient. The stimulator may be turned “on,” thusactivating the electrical stimulation to the appropriate nervous tissueassociated with a thoracic vertebral segment, by the patient whenfeelings of hunger are present. Alternatively, it is contemplated thatthe patient may use the stimulation in a continuous manner. Stillfurther, an external handheld device (a “patient programmer”) can beused by the patient to wirelessly communicate with the implantedstimulator system to initiate the electrical stimulation at anappropriate time.

In one embodiment, it is contemplated that treating gastrointestinaland/or eating disorders or conditions comprises spinal cord stimulationof nervous tissue associated with one or more areas associated with athoracic segment, which will cause an increase in expression ofneurotransmitters, neuromodulators and peptides or hormones associatedwith increased gastric motility. In another embodiment, it iscontemplated that treating gastrointestinal and/or eating disorders orconditions comprises causing an increase in expression ofneurotransmitters, neuromodulators or peptides associated with a feelingof fullness, for example glucagon-like peptide-1 (GLP-1) throughmodulation of spinal nervous tissue.

For patients suffering from anorexia nervosa or bulimia nervosa,complications of these eating disorders include gastrointestinalproblems such as substantial delays in gastric emptying as well asconstipation. These problems may give rise to significant medicalcomplications and may contribute to increased difficulties withrefeeding and weight restoration. It is contemplated that spinal cordstimulation may be used as part of ongoing therapy for anorexia nervosaor bulimia nervosa in order to normalize gastric function.

Further, biliary tract disorders, of the gall bladder or bile ducts, arealso contemplated as being treatable by the method of the presentinvention. For example, cholecystitis, biliary dyskinesia, andcholangitis may be treated by stimulation of the thoracic nerves. Yetfurther, hepatic disorders, such as cirrhosis, are contemplated as beingtreatable by the method of the present invention.

The therapeutic system or of the present invention is surgicallyimplanted in the predetermined sites as described in the above sections.One of skill in the art is cognizant that a variety of electrodes orelectrical stimulation leads may be utilized in the present invention.It is desirable to use an electrode or lead that contacts or conforms tothe target site for optimal delivery of electrical stimulation. One suchexample, is a single multi contact electrode with eight contactsseparated by 2½ mm each contract would have a span of approximately 2mm. Another example is an electrode with two 1 cm contacts with a 2 mmintervening gap. Yet further, another example of an electrode that canbe used in the present invention is a 2 or 3 branched electrode to coverthe predetermined site or target site. Each one of these three prongedelectrodes have four contacts 1-2 mm contacts with a center to centerseparation of 2 of 2.5 mm and a span of 1.5 mm

According to one embodiment of the present invention, the target site isstimulated using stimulation parameters such as, pulse width of about 1to about 500 microseconds, more preferable, about 1 to about 90microseconds; frequency of about 1 to about 50 to about 3,000 Hz, morepreferably, about 10 to about 350 Hz; and voltage of about 0.5 to about10 volts, more preferably about 1 to about 10 volts. It is known in theart that the range for the stimulation parameters may be greater orsmaller depending on the particular patient needs and can be determinedby the physician. Other parameters that can be considered may includethe type of stimulation for example, but not limited to acutestimulation, subacute stimulation, and/or chronic stimulation.

Applying electrical stimulation to the gastrointestinal tract can havethe effect of suppressing appetite but may also produce “intestinalhurry” where the food is passed through the gastrointestinal tract morequickly than normal so as to reduce the body's absorption of nutrients.Gastrointestinal tract hurry can be produced by stimulation of thestomach and/or small intestine

Gastrointestinal tract stimulation according to the invention may becontinuous, intermittent, or responsive to patient initiation orgastrointestinal tract activity detection.

Yet another object of the present invention is to stimulate the stomachand/or small intestine to produce gastrointestinal hurry where the speedof the passage of food through the gastrointestinal tract is increasedso as to reduce the absorption of nutrients as a means to achieve weightloss for obese patients.

Patient outcomes for patients treated by the methods and systems of thepresent invention may be tested by standard stomach emptying tests, suchas radioactive meal digestion, for example as described in U.S. Pat. No.6,548,043. Gastric motility may be tested by an antro-duodenal motilitystudy, in which a thin tube (one-eighth inch in diameter) is passedthrough the nose, down the esophagus, through the stomach and into theduodenum, the first part of the small intestine. Sensors in the tubemeasure the amount of pressure generated when the muscles of the stomachand intestine contract and squeeze tightly around the tube. The greaterthe contraction of the muscles, the greater the pressure sensed by thetube. All contractions are recorded by a computer for analysis.Contractions are recorded at rest for up to several hours and for one ortwo hours after a meal. Other contemplated test to study patientoutcomes include upper gastrointestinal x-rays, gastric emptying breathtests, and electrogastrograms

Patient outcomes may also be tested by health-related quality of life(HRQL) measures: Patient outcome measures that extend beyond traditionalmeasures of mortality and morbidity, to include such dimensions asphysiology, function, social activity, cognition, emotion, sleep andrest, energy and vitality, health perception, and general lifesatisfaction. (Some of these are also known as health status, functionalstatus, or quality of life measures.)

For purposes of this invention, beneficial or desired clinical resultsinclude, but are not limited to, alleviation of symptoms, alleviation ofpain, diminishment of extent of disease, stabilized (i.e., notworsening) state of disease, delay or slowing of disease progression,amelioration or palliation of the disease state, and remission (whetherpartial or total), whether objective or subjective.

While the invention has been described herein relative to a number ofparticularized embodiments, it is understood that modifications of, andalternatives to, these embodiments, such modifications and alternativesrealizing the advantages and benefits of this invention, will beapparent those of ordinary skill in the art having reference to thisspecification and its drawings. It is contemplated that suchmodifications and alternatives are within the scope of this invention assubsequently claimed herein, and it is intended that the scope of thisinvention claimed herein be limited only by the broadest interpretationof the appended claims to which the inventors are legally entitled.

Although example steps are illustrated and described, the presentinvention contemplates two or more steps taking place substantiallysimultaneously or in a different order. In addition, the presentinvention contemplates using methods with additional steps, fewer steps,or different steps, so long as the steps remain appropriate forimplanting an example stimulation system 10 into a person for electricalstimulation of the spinal cord.

VIII. Examples

The following examples are included to demonstrate preferred embodimentsof the invention. It should be appreciated by those of skill in the artthat the techniques disclosed in the examples which follow representtechniques discovered by the inventor to function well in the practiceof the invention, and thus can be considered to constitute preferredmodes for its practice. However, those of skill in the art should, inlight of the present disclosure, appreciate that many changes can bemade in the specific embodiments which are disclosed and still obtain alike or similar result without departing from the spirit and scope ofthe invention.

Example 1 Treatment of Gastroparesis

Five patient with gastroparesis were implanted with a spinal cordstimulator in the T5/T6 epidural space. After continuous stimulation for24-48 hours, the patients reported normal gastric emptying and bowelfunction.

Example 2 Treatment of Abdominal Pain

Patient with gastroparesis was implanted with a spinal cord stimulatorin the T5/T6 epidural space. After continuous stimulation for 48 hours,the patient reported a complete absence of abdominal pain andgastroparesis-related nausea.

REFERENCES

All patents and publications mentioned in the specifications areindicative of the levels of those skilled in the art to which theinvention pertains. All patents and publications are herein incorporatedby reference to the same extent as if each individual publication wasspecifically and individually indicated to be incorporated by reference.

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Although the present invention and its advantages have been described indetail, it should be understood that various changes, substitutions andalterations can be made herein without departing from the invention asdefined by the appended claims. Moreover, the scope of the presentapplication is not intended to be limited to the particular embodimentsof the process, machine, manufacture, composition of matter, means,methods and steps described in the specification. As one will readilyappreciate from the disclosure, processes, machines, manufacture,compositions of matter, means, methods, or steps, presently existing orlater to be developed that perform substantially the same function orachieve substantially the same result as the corresponding embodimentsdescribed herein may be utilized. Accordingly, the appended claims areintended to include within their scope such processes, machines,manufacture, compositions of matter, means, methods, or steps.

1.-9. (canceled)
 10. A method of treating gastroparesis, comprising:implanting at least one electrical lead of an electrical spinal cordstimulation system within the epidural space of a patient such that atleast one electrode of the electrical lead is disposed adjacent to nervetissue of the patient's spinal cord within a thoracic vertebral segment;selecting a plurality of operating parameters for the electrical spinalcord stimulation system that are effective for treating thegastrointestinal disorder; programming the electrical spinal cordstimulation system according to the plurality of operating parameters;and treating the patient's gastroparesis by increasing gastric motilityby activating the electrical spinal cord stimulation system to deliverelectrical pulses to the electrode adjacent to the nerve tissue withinthe thoracic vertebral segment.
 11. (canceled)
 12. The method of claim10 wherein the electrical spinal cord stimulation system deliverselectrical pulses on a temporary basis in response to receiving aninitiation signal from an external control device operated by thepatient.
 13. (canceled)
 14. The method of claim 10 wherein the pluralityof operating parameters include a pulse amplitude parameter, a pulsewidth parameter, and a pulse frequency parameter.
 15. The method ofclaim 10 wherein the pulse frequency parameter is within the range of10-350 Hz.
 16. The method of claim 10 wherein the lead comprises aplurality of electrodes and the plurality of operating parametersinclude an electrode configuration.
 17. The method of claim 10 whereinthe selecting comprises: temporarily delivering electrical pulsesaccording to the plurality of operating parameters to the electrodeadjacent to the nerve tissue within the thoracic vertebral segment; andmonitoring gastric activity that occurs while the temporarily deliveringis performed.
 18. The method of claim 17 wherein the monitoringcomprises: determining gastric motility by measuring pressure generatedby contraction of muscles of the stomach and/or small intestine.
 19. Themethod of claim 10 wherein the at least one electrode is implantedwithin the T5/T6 epidural space of the patient.
 20. The method of claim10, wherein the electrical spinal cord stimulation delivers electricalpulses on a substantially continuous basis.
 21. The method of claim 10,wherein the gastroparesis is associated with diabetes.